It has been postulated that a passively transferred immunological factor is responsible for the dengue hemorrhagic shock syndrome seen in primarily infected infants during the first year of life. The hypothesis was explored by adding dengue 2 virus to standardized cultrres of peripheral blood leukocytes (PBL) obtained from non-immune monkey or human donors with or without varying dilutions of anti-dengue 4 serum. D2V grew readily when final dilutions of anti-D-4 varied between 1:20 and 1:2500, but poorly, or not at all in cultures containing similar dilutions of normal serum. These dilutions of anti-D4 had no hemagglutination inhibiting or neutralizing activity against D2V. Human anti-Dl and anti-D3 prepared in monkeys and anti-Dl and anti-D4 enhanced the replication of D2V in monkey or human PBL. Anti-D2 prevented D2V infection at low dilutions, but at dilutions from 1:1000 to 1:10,000 enhanced virus growth. Purified anti-D4 IgG enhanced D2V infection. These observations suggest a dual role for IgG dengue antibodies: 1) Neutralization at high concentrations and 2) promotion of leukocyte infection at non-neutralizing dilutions. Future studies will focus on the leukocyte type(s) which support dengue replication, mechanism of penetration of virus-antibody complex and biologically active products which results from leukocyte infection. Immunologically enhanced replication of dengue virus in PBL may serve as a model for exploring causal mechanisms in SIDS.